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François Paraf

Publications and source records attributed to François Paraf.

18 recordsLinked to original sources
PubMed2006

[Prostatic sarcoma: Report of two cases].

Prostatic sarcomas are very rare tumours with a very poor prognosis. They may coexist with prostatic adenocarcinoma, in which case they are only diagnosed on histological examination of the operative specimen with identification of sarcoma on immunohistochemical analysis. Due to their rapidly invasive potential, they must be detect early in the course, particularly in young subjects. Certain clinical signs, such as obstructive urinary symptoms in a young man or rectal symptoms in an elderly man are suggestive of sarcoma. In this article, the authors report two cases of prostatic sarcoma surgically treated and present a review of the literature on this disease.

Adult↗
PubMed2005

Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor.

Antiangiogenesis or destruction of tumor neovessels is an effective strategy to prevent tumor growth. Endostatin, one of the many inhibitors of angiogenesis that have been discovered, has shown conflicting results in preclinical assays. We studied the therapeutic potential of lipid/DNA complexes consisting of cationic liposomes and an endostatin-coding plasmid (Endo cDNA/CLP) in an orthotopic osteosarcoma model in rats. Empty plasmid without the endostatin gene complexed with cationic liposomes served as control. Animals were treated intravenously three times a week starting on the day tumors were detectable by (18)FDG tomoscintigraphy. During treatment, tumor progression was followed by PET scan and angioscintigraphy, and the effects of antivascular therapy on primary tumor, metastases, and tumor vascular density were confirmed by histologic analysis. Our results demonstrate that therapy using Endo cDNA/CLP is associated with pronounced delay in tumor growth. Moreover, it effectively prevented the occurrence of lung metastases, the major reason for bad prognosis and death in osteosarcoma patients. This approach could be used as an adjuvant therapy for osteosarcoma.

Animals↗
PubMed2005

Intracranial granuloma and skull osteolysis: complication of a primary cutaneous cryptococcosis in a kidney transplant recipient.

Cryptococcosis is the third most common invasive fungal infection in organ transplant recipients after candidiasis and aspergillosis. It occurs almost exclusively in the late posttransplantation period (>6 months after the initiation of immunosuppression). Subclinical onset of meningitis is the usual clinical presentation. Despite initiation of therapy, the mortality rate associated with this infection in this patient population remains high. To the best of our knowledge, this report describes one of the first cases of a rare entity: a primary cutaneous cryptococcosis in a renal transplant recipient disclosed by skull osteomyelitis and pseudotumoral intracranial extension. Surgical debridement and azole antifungal therapy were performed. Ten months after the onset of treatment, the patient feels good, clinical examination findings are normal, and no sign of evolutive cryptococcosis is noted.

Abscess↗
PubMed2005

[Is tumour grade applicable to finasteride-treated prostate cancer?].

The treatment of prostate cancer by endocrine therapy induces histological changes of benign or malignant prostate glands. Treated cancers often have a more suspicious architecture, resulting in a higher Gleason score, while their nuclear grade (WHO) appears to be more reliable due to a reduction of the size of nuclei. Most authors appear to agree that cancers discovered by biopsy in patients treated with endocrine therapy should not be graded. A review of the literature appears to indicate that finasteride has less marked histomorphological consequences than other hormone-suppressor treatments and could have a lesser effect on the Gleason score. This paper, based on a review of the literature on this subject, emphasizes: (1) the extent of histological changes after androgen deprivation endocrine therapy; (2) histological changes after Finasteride and the difficulties of histological interpretation, particularly the risk of overestimating the Gleason histoprognostic score; (3) the need for urologists to indicate any treatment by 5-alpha-reductase inhibitors or androgen deprivation when requesting histological examination; (4) the value of collecting and documenting cases observed in the Uropathology Club in collaboration with the Oncology committee of the Association Française d'Urologie.

5-alpha Reductase Inhibitors↗
PubMed2004

Human chorionic gonadotrophin beta expression in malignant Barrett's oesophagus.

BACKGROUND: Human chorionic gonadotrophin beta (hCGbeta) is expressed in several non-trophoblastic tumours, and this is usually associated with aggressive behaviour. Little is known about hCGbeta expression in Barrett's adenocarcinoma. MATERIALS AND METHODS: We determined the hCGbeta profile in a large series of surgically resected Barrett's adenocarcinoma (a) at mRNA level using real-time quantitative reverse-transcription polymerase chain reaction analysis and (b) at protein level using immunohistochemistry with a polyclonal antibody and with a monoclonal antibody specific for free hCGbeta. We then sought links between the hCGbeta protein expression pattern and clinical and pathological parameters, including patient outcome as well as vascular endothelial growth factor (VEGF) expression. RESULTS: hCGbeta protein expression was observed in 43 of 76 (57%) Barrett's adenocarcinomas. We showed a strong correlation between hCGbeta protein abundance and CGB mRNA level. We observed a statistical link between hCGbeta protein expression and infiltrative tumour type ( P=0.023), perineural neoplastic invasion ( P=0.007) and VEGF protein expression ( P=0.016). hCGbeta expression tended to be associated with a poor outcome (16% versus 36% survival 8 years after resection). CONCLUSION: Expression of hCGbeta correlates with specific infiltrative characteristics and is associated with higher VEGF expression. Both molecules may play a co-ordinated role in the development of Barrett's adenocarcinomas.

Adenocarcinoma↗
PubMed2004

Expression of inflammatory secretory phospholipase A2 and cytosolic phospholipase A2 in premalignant and malignant Barrett's oesophagus.

AIMS: To establish the prevalence of inflammatory secretory phospholipase A2 (sPLA2) and cytoplasmic phospholipase A2 (cPLA2) expression in a surgical series of Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis. METHODS: sPLA2 and cPLA2 were analysed by means of immunohistochemistry in surgical specimens of 67 and 73 cases of Barrett's adenocarcinomas, respectively. Barrett's mucosa was analysed in 31 cases. RESULTS: Expression of sPLA2 was detected in 48% of Barrett's mucosa negative for intraepithelial neoplasia and 63% of Barrett's adenocarcinoma. Semi-quantitative analysis revealed a significant increase in sPLA2 expression between Barrett's mucosa negative for intraepithelial neoplasia and adenocarcinoma. cPLA2 expression was detected in 18% of Barrett's adenocarcinoma. An inverse correlation was found between cPLA2 expression and depth of tumour infiltration, neoplastic vascular invasion and neoplastic perineural invasion. Survival analysis showed no significant prognostic value for sPLA2 and cPLA2. CONCLUSION: sPLA2 is frequently expressed in Barrett's oesophagus. The increasing expression of sPLA2 that we observed from Barrett's mucosa to adenocarcinoma suggests that sPLA2 could be involved in Barrett's carcinogenesis. In contrast, cPLA2 expression is less frequently observed in Barrett's oesophagus and is inversely associated with aggressive pathological features of the tumours.

Adenocarcinoma↗
PubMed2004

[Hirschsprung's disease: practical considerations].

Hirschsprung's disease (1/5000 live births) is defined by the congenital absence of neuronal cells in the nervous plexuses in the distal part of the digestive tract. The disease affects the rectum and sigmoid colon in 80% of cases, or is more extensive. Hirschsprung's disease is suspected in cases of low gastrointestinal obstruction in the neonatal period, or in cases of chronic severe constipation in childhood. It is diagnosed by pathological examination of rectal biopsies that include the submucosa. After standard staining, multiple sections are scrutinized for neuronal cells. Acetylcholinesterase staining is performed on a frozen fragment to demonstrate the hyperplasia of cholinergic fibers that is very suggestive of Hirschsprung's disease. This hyperplasia decreases from the rectum to the splenic flexure of the colon. Hyperplasia of extrinsic nerve fibers and rarefaction of neuromuscular junctions in Hirschsprung's disease may be demonstrated immunohistochemically. Differential diagnosis includes chronic intestinal pseudo-obstructions. The treatment for Hirschsprung's disease is, most often, anastomosis of the normally innervated gut to the anal canal. Peri- or pre-operative biopsies assist surgery, but their interpretation is difficult in the transitional zone. The examination of the surgical specimen allows measurement of the aganglionic segment and transitional zone. Different genes (RET, most often) may be involved in sporadic or familial Hirschsprung's disease. Hirschsprung's disease is associated with other digestive or extra-digestive abnormalities in 5 to 30% of patients. Associated abnormalities may delay the diagnosis and treatment of Hirschsprung's disease.

Biopsy↗
PubMed2003

Microsatellite instability in colorectal carcinoma. The comparison of immunohistochemistry and molecular biology suggests a role for hMSH6 [correction of hMLH6] immunostaining.

CONTEXT: Microsatellite instability (MSI) due to defective mismatch repair (MMR) genes has been reported in the majority of colorectal tumors from patients with hereditary nonpolyposis colorectal cancer syndrome and in 10% to 15% of sporadic colorectal cancers. The identification of cancers associated with MSI requires classical molecular testing as the gold standard. OBJECTIVE: The aim of this study was to evaluate the role of immunohistochemistry with antibodies directed against 4 MMR proteins as a screening tool for carcinomas with MSI. METHODS: In this study, 204 formalin-fixed, paraffin-embedded colorectal carcinomas were examined for MMR protein expression (hMLH1, hMSH2, hMSH6, and hPMS2) and analyzed for MSI (MSI-H indicates at least 2 of 6 markers affected). These results were correlated with histopathologic parameters. RESULTS: Immunohistochemical analysis revealed that loss of expression of at least 1 protein was present in 17% of cases. One hundred percent of carcinomas that showed high instability (MSI-H) showed loss of expression of hMLH1, hMSH2, or hMSH6. Loss of expression of 2 proteins was present in 59.4% of MSI-H cases, with only 2 combinations, namely, hMLH1/hPMS2 and hMSH2/hMSH6. Isolated loss of hMSH6 expression was present in 2 MSI-H cases. CONCLUSIONS: These findings confirm that examination of MMR protein expression by immunohistochemistry is a simple method to diagnose colorectal cancer with MSI. Our data suggest that the study of hMSH6 may be useful, in addition to hMLH1 and hMSH2. Moreover, immunohistochemistry could represent a screening method with which to direct research on the mutations of MMR genes observed in hereditary nonpolyposis colorectal cancer syndrome.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Influence of host-recipient origin on clinical aspects of posttransplantation lymphoproliferative disorders in kidney transplantation.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) is a well-known complication of immunosuppression associated with solid organ transplantation. The donor or host origin of PTLD may influence the outcome of the disease as it has been reported that a donor origin may be associated with a better prognosis. The aim of the study was to determine the origin (recipient or donor) of 12 PTLD occurring in kidney transplant recipients and to correlate the results with clinical findings. METHODS: Origin of PTLD was determined using HLA DRB1 molecular typing, analysis of multiple short-tandem repeat microsatellite loci, and HLA class I antigen expression by immunohistochemistry. RESULTS: Combining the three techniques, we found that eight cases originated from the recipient and four cases originated from the donor. The results of the three techniques were concordant and altogether assigned the origin of the tumors. All the donor-origin PTLD were strictly localized to the kidney graft, developed after a mean time of 5 months after transplantation, and regressed after reduction of immunosuppression. In contrast, seven of the eight recipient-origin PTLD presented as multisystemic disease, occurred a mean time of 75.7 months after the transplantation, and had a worse outcome (mortality, five deaths of eight patients, 62.5%). CONCLUSIONS: These results suggest that PTLD originating from the donor arise in the first year after transplantation into the graft, and that recipient-origin PTLD develop later as an invasive disease. Because it permits simultaneously the analysis of cell morphology and tumor origin, immunohistochemistry is a more reliable technique in the case of graft tumors associated with allograft rejection. The determination of the origin of the tumors seems to be of value in the management of PTLD to predict the outcome and to adapt therapy.

Adult↗
PubMed2002

[Duodenal bleeding revealing a renal cell carcinoma].

The pancreas is an uncommon site of metastasis from renal cell carcinoma. The metastasis is generally diagnosed during the follow-up of patients who underwent nephrectomy for renal cell carcinoma. In our observation, duodenal bleeding led to the diagnosis of both pancreatic metastasis and renal carcinoma. The diagnosis of pancreatic metastasis should be suspected when a pancreatic mass is associated with past or synchronous renal carcinoma. The outcome after resection of pancreatic metastasis is better than after resection of pancreatic adenocarcinoma. Surgical resection of pancreatic metastasis should be considered when possible.

Carcinoma, Renal Cell↗
PubMedDate not supplied

In vivo follow-up of rat tumor models with 2-deoxy-2-[F-18]fluoro-D-glucose/dual-head coincidence gamma camera imaging.

UNLABELLED: Before studying the impact of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) imaging with a dual-head coincidence gamma camera (DHC) for the follow-up of animal tumor models, we wanted to optimize this technique. METHODS: Three different animal tumor models (osteosarcoma, melanoma, and breast cancer) were studied after FDG injection. Dynamic and dual time point FDG/DHC imaging were studied from one hour to five hours postinjection. In vitro tumor cell FDG uptake was assessed in eight different tumor cell lines. In one model (osteosarcoma), tumor growth, lung metastasis emergence, and survival were assessed by classical clinical follow-up and compared to FDG imaging in a control group (n = 6) and in a group treated by endostatin liposome complexes (n = 6). RESULTS: Images obtained five hours after injection were more reliable for tumor growth follow-up than standard images (one hour). In vitro tumor cell FDG uptake confirmed in vivo imaging studies. In eight different tumor cell lines the FDG uptake was higher after five hours incubation than after one hour (p < 0.002). With FDG follow-up, we found that FDG uptake was strongly correlated with survival and that lung metastasis larger than 5 mm could be detected. CONCLUSION: Using the optimization proposed above, DHC/FDG functional imaging seems to be a powerful tool to study rat tumor models and to help develop novel cancer therapies.

Animals↗
PubMedDate not supplied

[Hepatic metastatic miliaria from a malignant melanoma: 2 case reports].

Malignant melanoma of uveal or cutaneous origins are diseases which may run a fulminant metastatic course immediately or after a prolonged disease-free period. The liver is the most common initial site of metastatic involvement. Nevertheless, hepatic metastatic miliaria spread is rare. In these cases, morphological studies are normal and only biological abnormalities including icteric cholestasis and hepatocellular insufficiency may suggest this diagnosis. We report two cases of hepatic metastatic miliaria from malignant melanoma diagnosed by percutaneous liver biopsy.

Aged↗
PubMedDate not supplied

Value of microsatellite instability typing in detecting hereditary non-polyposis colorectal cancer. A prospective multicentric study by the Association Aquitaine Gastro.

AIM OF THE STUDY: To detect hereditary non-polyposis colorectal cancer (HNPCC) patients with a strategy combining clinical selection (patient age at onset of cancer less than 50 years or family history of HNPCC tumors) and microsatellite instability typing plus immunohistochemistry, leading to mismatch repair (MMR) germline mutation analysis. METHODS: Tumors were screened for microsatellite instability (MSI) and for hmlh1 and hmsh2 immunohistochemical expression. Germline mutation analysis was performed to search for MLH1 and MSH2 mutations in patients with MSI-High and MSI-Low tumors. RESULTS: 197 adenocarcinomas were studied: 164 patients were< or =50 years old, 33 were older than 50 years but had a family history of HNPCC tumors. Fifty tumors (25.4%) were MSI-High, 10 were MSI-Low (5.1%), and 130 were MS-Stable (66%). MSI typing was inconclusive in 7 (3.5%). Immunohistochemistry screening was performed on 165 tumors: sensitivity was 63.6%, specificity was 99%. Germline mutation analysis was performed in 33/60 MSI-High or Low tumors: 23 mutations were noted (70% of the tested patients). CONCLUSION: This proposed strategy of determining microsatellite instability in young colorectal cancer patients or in patients with a family history of HNPCC tumors led to an increased frequency in the detection of MMR germline mutations.

Adenocarcinoma↗
PubMedDate not supplied

A new orthotopic model of human breast cancer in immunocompetent rats.

BACKGROUND: Breast cancer is the first cause of mortality by cancer in women in North America and Western Europe. For non-estrogen-dependent tumors as well as for metastatic cancers, current therapies are of limited efficacy. Several animal models have been described but they are imperfect as they are poorly representative of what occurs in real tumors. To overcome some of these limitations, we describe a new orthotopic model of estrogen-independent breast cancer in immunocompetent rats treated with cyclosporin A (CysA). MATERIALS AND METHODS: Injection of cell suspensions of human breast MDA-MB-231 cancer cells into the mammary fat pad or subcutaneous grafts of solid tumor sections were performed on Sprague Dawley rats receiving intraperitoneally 35 mg/kg of CysA. Tumor growth was measured and monitored by scintigraphy using 18FDG and 99mTc-MIBI. RESULTS: In both models, tumors grew well but growth rates were different. Cell suspension injections gave rise to tumors with a higher growth rate and the tumors obtained infiltrated the mammary and giving results closer to human pathology. CONCLUSION: This animal model with injected cells may provide a new adequate tool for studying breast cancer and developing new therapy strategy.

Animals↗
PubMedDate not supplied

Logistic regression model of the clinical response to 5-fluorouracil based chemotherapy for metastatic colorectal cancer patients.

Several genes have been involved in drug resistance but none are currently used in the drug decision process. To address this problem, mRNA levels were measured for the 5-fluorouracil metabolism-related genes, thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumor samples of 40 patients with synchronous metastatic colon cancer by quantitative RT-PCR. Drug response and overall survival were also obtained for each patient. A logistic regression model was defined to calculate a response predicting score (RPS) with gene expression levels. This RPS split responders from nonresponders as, at the best statistical threshold (0.35), the area of receiver operating characteristic (ROC) curve established with this method was 0.82 and sensitivity and specificity were respectively 100% and 65.4%. Furthermore patients with scores above 0.35 tended to have better overall survival than those with a score less than 0.35 (p = 0.09).

Aged↗